This program project represents a multidisciplinary approach to problems in allograft and tumor immunity; it attempts to approach the problems of antigen recognition and immune response to normal histocompatibility and tumor antigens by studying the genetic control of alloantigens, the nature of the allo- and tumor antigens as components of the lymphocyte or tumor cell membrane, the cellular response to these various antigenic stimuli, and the physiological behavior of the membrane antigens as it relates to the immune response to the cells carrying the antigen. The program is composed of two research parts which are intimately interdependent and complementary: one, genetic and biological studies and two, biochemical studies of lymphocyte and tumor cell membranes, both in relation to allograft and tumor immunity. The first part is concerned with a study of the genetic control of normal histocompatibility antigens, primarily those controlled by the major histocompatibility complex (MHC), at both the stuctural and functional level. The MHC will be used as a model for tumor associated antigens and attempts will be made to extrapolate use of the in vitro models developed for the allograft response to the study of tumor associated antigens. The second part envisages a detailed biochemical study of the membranes of normal lymphocytes and leukemic cells. The purpose of such a study is not primarily to understand the chemistry of membranes and membrane components but rather to learn more about the genetic control of lymphocyte membrane structure and its relation to immune response, leukemia-associated membrane changes, and the fundamental mechanisms underlying immune response to leukemia and other tumors.